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Background. Activity against Gram negative bacteria, including Pseudomonas aeruginosa, is required for first line antibiotic therapy in patients with febrile neutropenia.Aim. To study in vitro activity of cefepime / sulbactam and biapenem against Enterobacterales and P. aeruginosa strains in patients with bloodstream infection and hematologic diseases.Materials and methods. Susceptibility of cefepime / sulbactam and biapenem in comparison to anibiotics used for febrile neutropenia was studied among Escherichia coli (n = 100), Klebsiella pneumoniae (n = 100), Enterobacter cloacae complex (n = 30), and P. aeruginosa (n = 70) isolated from blood culture (2017–2021) from patients with hematological diseases and infection in 4 Russian hospitals. Activity was determined by broth microdilution method, interpretation was according to Clinical and Laboratory Standards Institute (CLSI, 2022) and European Committee on Antimicrobial Susceptibility Testing (EUCAST , 2022) criteria, for cefepime / sulbactam we used cefepime criteria. The values of the minimum inhibitory concentration (MIC), MIC50 and MIC90 were studied.Results. MIC90 of cefepime / sulbactam were lower in comparison with piperacillin / tazobactam for E. coli without extended spectrum beta-lactamase (ESBL) production (0.125 μg / mL vs 1 μg / mL), K. pneumoniae without ESBL-production (0.125 μg / mL vs 2 μg / mL), K. pneumoniae with ESBL-production (32 μg / mL vs 128 μg / mL) with comparable frequency of resistant strains. For P. aeruginosa, preference of cefepime / sulbactam over piperacillin / tazobactam were found both by lower MIC90 (8 μg / mL vs 32 μg / mL) and by lower frequency of resistant strains according to EUCAST criteria (4.3 % vs 25.7 %). The MIC90 values of cefepime / sulbactam compared to cefepime and ceftazidime were 4 times lower for K. pneumoniae with ESBL-production and for Enterobacter cloacea complex, 2–4 times lower for P. aeruginosa, 64 times lower for E. coli with ESBL production.Values of biapenem MIC90 for E. coli without and with ESBL-production (0.032 μg / mL) were in intermediate position between meropenem and imipenem; for K. pneumoniae without ESBL-production – identical to imipenem (0.064 μg / mL), for K. pneumoniae with ESBL – minimal (0.064 μg / mL) against imipenem and meropenem; for E. cloacae – comparable to meropenem (0.032 μg / mL). For P. aeruginosa without carbapenemase production, the MIC50 / MIC90 values of biapenem (0.125 / 16 μg / mL) were minimal compared to meropenem (0.25 / 64 μg / mL) and imipenem (0.5 / 64 μg / mL).Conclusion. The favorable in vitro activity of cefepime / sulbactam and biapenem are fully comply with the requirements for febrile neutropenia.
Background. Activity against Gram negative bacteria, including Pseudomonas aeruginosa, is required for first line antibiotic therapy in patients with febrile neutropenia.Aim. To study in vitro activity of cefepime / sulbactam and biapenem against Enterobacterales and P. aeruginosa strains in patients with bloodstream infection and hematologic diseases.Materials and methods. Susceptibility of cefepime / sulbactam and biapenem in comparison to anibiotics used for febrile neutropenia was studied among Escherichia coli (n = 100), Klebsiella pneumoniae (n = 100), Enterobacter cloacae complex (n = 30), and P. aeruginosa (n = 70) isolated from blood culture (2017–2021) from patients with hematological diseases and infection in 4 Russian hospitals. Activity was determined by broth microdilution method, interpretation was according to Clinical and Laboratory Standards Institute (CLSI, 2022) and European Committee on Antimicrobial Susceptibility Testing (EUCAST , 2022) criteria, for cefepime / sulbactam we used cefepime criteria. The values of the minimum inhibitory concentration (MIC), MIC50 and MIC90 were studied.Results. MIC90 of cefepime / sulbactam were lower in comparison with piperacillin / tazobactam for E. coli without extended spectrum beta-lactamase (ESBL) production (0.125 μg / mL vs 1 μg / mL), K. pneumoniae without ESBL-production (0.125 μg / mL vs 2 μg / mL), K. pneumoniae with ESBL-production (32 μg / mL vs 128 μg / mL) with comparable frequency of resistant strains. For P. aeruginosa, preference of cefepime / sulbactam over piperacillin / tazobactam were found both by lower MIC90 (8 μg / mL vs 32 μg / mL) and by lower frequency of resistant strains according to EUCAST criteria (4.3 % vs 25.7 %). The MIC90 values of cefepime / sulbactam compared to cefepime and ceftazidime were 4 times lower for K. pneumoniae with ESBL-production and for Enterobacter cloacea complex, 2–4 times lower for P. aeruginosa, 64 times lower for E. coli with ESBL production.Values of biapenem MIC90 for E. coli without and with ESBL-production (0.032 μg / mL) were in intermediate position between meropenem and imipenem; for K. pneumoniae without ESBL-production – identical to imipenem (0.064 μg / mL), for K. pneumoniae with ESBL – minimal (0.064 μg / mL) against imipenem and meropenem; for E. cloacae – comparable to meropenem (0.032 μg / mL). For P. aeruginosa without carbapenemase production, the MIC50 / MIC90 values of biapenem (0.125 / 16 μg / mL) were minimal compared to meropenem (0.25 / 64 μg / mL) and imipenem (0.5 / 64 μg / mL).Conclusion. The favorable in vitro activity of cefepime / sulbactam and biapenem are fully comply with the requirements for febrile neutropenia.
The objective was to study the risk factors, outcomes of infections caused by colistin-resistant K. pneumonia (CRKP) and to evaluate the sensitivity of these microorganisms to antibacterial agents to determine the most adequate antibiotic therapy options.Materials and methods. Klebsiella pneumoniae strains isolated in the ICU of an acute care hospital between October 2020 and August 2022 were included in the study. Microorganisms were identified using an automatic analyzer PHOENIX. The determination of antibiotic sensitivity was studied by the method of serial micro-dilutions in agar with the determination of MIC EUCAST criteria were used to interpret sensitivity. Detection of carbapenemases was carried out by PCR. Clinical efficacy of starter therapy was evaluated as recovery/improvement and no effect.Results. The infection was characterized by a severe course in 58.9 % of patients, with SOFA scores ranging from 1 to 16 points (mean 5.8 points). 88.2 % of patients had received prior antibiotics, most commonly carbapenems. CRKP infections occurred more frequently in older men with comorbidity. The clinical efficacy of initial antibiotic therapy was 41.2 %. In 47.1 % of cases, there was no effect, which required adjustment of therapy. Excluding patients in whom it was impossible to evaluate the effect, eradication was achieved in 33.3 % of patients. 64.6 % of patients were discharged or transferred to another hospital; 6 patients died between 5 and 41 days after diagnosis of CRKP infection. Fatal outcome was more frequent in women ( p=0.042), patients with higher comorbidity index (p=0.027), in case of sepsis and/or septic shock ( p=0.011), and in earlier detection of CRKP after hospitalization ( p<0.001).Conclusion. The efficacy of initial antibiotic therapy after detection of CRKP infection has been shown to be associated with patient survival and reduced risk of mortality with an odds ratio of 3.5. We also identified risk factors for mortality in CRKP infection: comorbidity, sepsis, duration of hospitalization and female gender.
The objective was to evaluate the clinical effectiveness and safety of biapenem (Bianem–AF drug) in the treatment of severe forms of infection in ICU patients.Materials and methods. The prospective observational study. At the first stage, microbiological testing of strains (n = 51) isolated from patients in ICU of the Scientific and Clinical Center of Anesthesiology and Intensive Care of the Pavlov University was performed to determine sensitivity to meropenem and biapenem by serial dilution method with the determination of MIC (Minimal Inhibitory Concentration). The genes of serine and metallocarbapenemases were detected by PCR method. At the second stage, patients over 18 years old with the site of infection that required surgical treatment and with clinical and laboratory signs of sepsis were included (n = 19: 11 females, 8 males, mean age 63.4 years). These patients received therapy with biapenem 600 mg every 12 hours as extended infusions over 1 hours (after bolus injection for the first 24 hours). Daily assessment of the severity of the inflammatory reaction and organ dysfunction was conducted to all patients included in the study. Microbiological analysis of biological material obtained from the site of infection has been obtained. Clinical effectiveness was evaluated as recovery/improvement or lack of effect. Adverse effects were recorded.Results. Among 51 isolates of microorganisms: 27 (52.9%) Klebsiella pneumonia, 16 (31%) strains of other representatives of the order Enterobacteriales, 8 (15,6%) non-fermenting gram-negative microorganisms. 48% of Klebsiella pneumoniae isolates were resistant to meropenem and biapenem. All of them had serine (class A and D) and metallo-carbapenemase (class B) genes, as well as their combination. Of the 16 strains of other representatives of the order Enterobacteriales, only 2 (12.5%) were resistant to meropenem and biapenem. Resistance to carbapenems in the non-fermenting gram-negative microorganisms reached 87.5%. The proportion of ESBL producers among carbapenem-sensitive Enterobacteriales reached 93%. The response to biapenem therapy was received in 100% of patients. A day after the start of biapenem administration, a decrease in the level of procalcitonin was noted from 4.65 ng/ml (1.26; 18.8) to 2.2 (1.3; 16.2), after 72 hours – to 1.9 (0.8; 5.0) ng/ ml, by the 7th day – to 0.6 (0.3; 2.5) ng/ml. The median SOFA score decreased from 3.0 (1.5; 4.0) after 24 hours to 2.0 (0,5; 3,5). The average duration of antibacterial therapy was 6 days, the duration of stay in the ICU was two days, and the duration of hospitalization was 9.5 days. There were no adverse effects when using biapenem.Conclusion. Given the high prevalence of ESBL producers and Pseudomonas aeruginosa strains in hospitals, the more favorable safety profile of biapenem compared to other carbapenems, Biapenem appears to be a justified choice for initial empirical therapy MDR sepsis.
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